The goal of the proposed research is to advance our understanding of the storage, maintenance, and retrieval of information in visual working memory. Our guiding hypothesis is that these functions involve the synchronous, and causal, interactions of neuronal populations located in prefrontal, posterior parietal, and inferior temporal cortical regions. Our research plan, based on an extensive body of preliminary studies supported by a previous R21 award, consists of two sets of experiments addressing three specific aims. In the first experiment, we will train macaque monkeys to perform an oculomotor delayed match-to-sample task in which memory load will be manipulated by changes in task duration and the inclusion of distractors. This study will enable us to test specific hypotheses regarding the neural mechanisms mediating the storage and maintenance of information in visual working memory. In the second experiment, another set of monkeys will be trained to perform a delayed match-to-sample task in which they must actively retrieve either the shape or the color of a sample object following a rule-based cue. This experiment will enable us to test specific hypotheses regarding the neural mechanisms mediating the active retrieval of information from visual working memory. In both experiments, we will perform long-term measurements of neuronal activity (i.e. unit activity and local field potentials) from up to 32 independently movable microelectrodes in prefrontal, posterior parietal, and inferior temporal cortical areas while the monkeys perform the behavioral tasks. Once the data are collected, we will apply a comprehensive battery of statistical analyses to test specific hypotheses regarding the storage, maintenance and retrieval of information in visual working memory. These analyses will characterize the spatiotemporal statistical relations between groups of simultaneously recorded neurons, between neurons and local field potentials, and between local field potentials. The results will allow us to test hypotheses concerning the synchronous neuronal interactions that occur both within and between cortical areas in support of visual working memory function. We anticipate that the proposed studies will produce new insights into the dynamics of synchronous activity thought to underlie the representation and utilization of visual information in working memory. The knowledge gained from these studies will provide an important framework for understanding synchronous functional relations in the brain that may be important in the diagnosis of pathological conditions, such as Alzheimer's disease, autism, and schizophrenia, in which these relations have already been demonstrated to be deficient. PUBLIC HEALTH RELEVANCE: Disturbances of attention and working memory, and the changes in synchronous cortical activity that accompany them, are a hallmark of human psychiatric conditions including Alzheimer's disease, Autism, Attention Deficit Hyperactivity Disorder, and Schizophrenia. Analyses of disturbances in cortico-cortical synchronization hold the promise of providing critical diagnostic measures for a wide variety of cognitive disturbances. Hence, an improved understanding of the neural mechanisms mediating working memory and the task-dependent synchronization of cortical activity will have a significant impact on the development of treatments for a wide variety of neuropsychiatric disorders.